Identification of microfilariae (MF) in peripheral blood provides a definitive diagnosis of lymphatic filariasis. However, this method is insensitive for detection of prepatent or amicrofilaremic infections. Recent reports have shown that recombinant Brugia malayi antigens BmM5 and BmMl4 may be useful for antibody diagnosis of lymphatic filariasis in humans. The purpose of this study was to examine the kinetics and specificities of antibody responses to these antigens in experimentally infected rhesus monkeys. Fourteen animals were infected with single or multiple injections of B. malayi L3. All infected animals produced antibodies to both recombinant antigens by 4-8 wks postinoculation, before the onset of MF patency at 10-12 wks. This included animals that failed to develop patent infections. Antibody levels declined over time, but increased again in animals that were reinjected with L3. Antibody responses to BmMl4 tended to be higher than those to BmM5 but the kinetics of both antigens were similar and significantly correlated. No correlation was observed between antibody levels and MF densities or the development of lymphedema in rhesus monkeys. Antibody levels to BmM14 also were detected in sera from only rhesus monkeys with Wuchereria bancrofti infection and not those with Loa loa or Onchocerca volvulus, suggesting the specificity of BmMl4 for detection of lymphatic filariasis. These encouraging results obtained in rhesus monkeys suggest that assays for antibodies to BmM5 and BmMl4 may be very useful for detecting prepatent, patent and mature amicrofilaremic B. malayi infections in humans.